Journal of Clinical and Translational Hepatology最新文献

{"title":"Exosome-mediated Crosstalk in the Tumor Immune Microenvironment: Critical Drivers of Hepatocellular Carcinoma Progression.","authors":"Yifei Ge, Lixue Jiang, Qingfu Dong, Yi Xu, Judy Wai Ping Yam, Xiangyu Zhong","doi":"10.14218/JCTH.2024.00302","DOIUrl":"10.14218/JCTH.2024.00302","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a significant global health issue, ranking as the sixth most prevalent malignancy and the fourth leading cause of cancer-related mortality worldwide. Despite advancements in therapeutic strategies, mortality rates for HCC remain high. The tumor immune microenvironment (TIME) plays a vital role in HCC progression by influencing tumor cell survival and growth. Recent studies highlight the essential role of exosomes in mediating intercellular communication within the TIME, particularly in interactions among tumor cells, immune cells, and fibroblasts. These interactions drive critical aspects of tumor development, including immune escape, angiogenesis, drug resistance, and metastasis. A detailed understanding of the molecular mechanisms by which exosomes modulate the TIME is essential for developing targeted therapies. This review systematically evaluated the roles and regulatory mechanisms of exosomes within the TIME of HCC, examining the impact of both HCC-derived and non-HCC-derived exosomes on various cellular components within the TIME. It emphasized their regulatory effects on cell phenotypes and functions, as well as their roles in HCC progression. The review also explored the potential applications of exosome-based immunotherapies, offering new insights into improving therapeutic strategies for HCC.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 2","pages":"143-161"},"PeriodicalIF":3.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium Butyrate Inhibits Necroptosis by Regulating MLKL via E2F1 in Intestinal Epithelial Cells of Liver Cirrhosis.","authors":"Yimeng Zhou, Yang Ding, Yanwei Li, Qiuju Sheng, Chao Han, Yaoxin Fan, Ziyi Wang, Bingchao Lu, Xiaoguang Dou, Chong Zhang","doi":"10.14218/JCTH.2024.00221","DOIUrl":"10.14218/JCTH.2024.00221","url":null,"abstract":"<p><strong>Background and aims: </strong>Necroptosis is critical for regulating intestinal epithelial cells (IECs). Butyric acid (BA), produced during intestinal microbial metabolism, protects the intestinal epithelial barrier. However, whether necroptosis occurs in IECs during liver cirrhosis and whether sodium butyrate (NaB) can regulate necroptosis have not yet been reported. In this study, we aimed to investigate whether IECs undergo necroptosis in cirrhosis and whether NaB can regulate necroptosis and the related regulatory mechanisms.</p><p><strong>Methods: </strong>Serum levels of RIPK3, MLKL, and Zonulin, as well as fecal BA levels, were measured and correlated in 48 patients with liver cirrhosis and 20 healthy controls. A rat model of liver cirrhosis was established, and NaB was administered. The expressions of MLKL, p-MLKL, and tight junction proteins were measured. We conducted an <i>in vitro</i> investigation of the effect of NaB on necroptosis in the HT29 cell line.</p><p><strong>Results: </strong>Serum levels of RIPK3, MLKL, and Zonulin in the liver cirrhosis group were higher, while fecal BA levels were lower than those in the control group. Zonulin levels were positively correlated with RIPK3 and MLKL levels, while fecal BA levels were negatively correlated with serum MLKL levels, but not with RIPK3 levels. NaB reduced the mRNA and protein expression of MLKL but had no effect on RIPK1 and RIPK3 in vitro. Rescue experiments demonstrated that NaB inhibited necroptosis through E2F1-mediated regulation of MLKL.</p><p><strong>Conclusions: </strong>NaB alleviates intestinal mucosal injury and reduces necroptosis in IECs in liver cirrhosis. It also inhibits the necroptosis of IECs and protects the intestinal barrier by reducing E2F1 expression and downregulating MLKL expression levels. These results can be employed to develop a novel strategy for treating complications arising from liver cirrhosis.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 2","pages":"105-117"},"PeriodicalIF":3.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ursodeoxycholic Acid for the Management of Drug-induced Liver Injury: Role of Hepatoprotective and Anti-cholestatic Mechanisms.","authors":"Fernando Bessone, Geraldine L Hillotte, Norberto Tamagnone, Daiana Arnedillo, Marcelo G Roma","doi":"10.14218/JCTH.2024.00325","DOIUrl":"10.14218/JCTH.2024.00325","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) is a harmful reaction to medications, herbs, and dietary supplements that results in liver dysfunction. Based on the distinct clinical patterns of liver damage, DILI can be categorized into hepatocellular, cholestatic, and mixed types. Hepatocellular DILI is linked to inflammation, apoptosis, and necrosis, while cholestatic DILI is commonly associated with bile plugs and, in rare cases, ductopenia. Ursodeoxycholic acid (UDCA) is the therapeutic agent most widely used for the treatment of cholestatic hepatopathies of diverse etiologies and has been mainly used as a supportive treatment in cholestatic DILI. In this review, we presented a more structured and systematic framework for the potential application of this hepatoprotective agent across a broader range of DILI scenarios. A MEDLINE search of the literature from 1995 to the present retrieved 41 preliminary clinical studies suggesting that UDCA may offer curative and preventive benefits for hepatocellular DILI as well. This aligns with preclinical studies in rodents, showing beneficial effects of UDCA in experimental DILI irrespective of the clinical patterns of injury involved. This could be due to the broad range of potentially beneficial effects of UDCA, which may address the various types of liver damage with different causes and mechanisms seen in all forms of DILI. UDCA's beneficial properties include anticholestatic, antioxidant, anti-inflammatory, anti-apoptotic, anti-necrotic, mitochondrial protective, endoplasmic reticulum stress-relieving, and immunomodulatory effects. Controlled studies with systematic use of standardized causality assessments are eagerly awaited to properly validate the use of UDCA in DILI. Meanwhile, we hope this article helps clarify and systematize the use of this versatile and safe hepatoprotective medication for different types of liver toxicity.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 2","pages":"162-168"},"PeriodicalIF":3.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral Blood CD4⁺/CD8⁺ T Cell Ratio Predicts HBsAg Clearance in Inactive HBsAg Carriers Treated with Peginterferon Alpha.","authors":"Fengping Wu, Chenrui Liu, Ling He, Yikai Wang, Xin Zhang, Miaoxian Li, Rui Lu, Pei Kang, Mei Li, Yaping Li, Xiaoli Jia, Shuangsuo Dang","doi":"10.14218/JCTH.2024.00240","DOIUrl":"10.14218/JCTH.2024.00240","url":null,"abstract":"<p><strong>Background and aims: </strong>T lymphocytes play a pivotal role in resolving hepatitis B virus infection. This study aimed to investigate the dynamics of peripheral blood T lymphocyte subsets during peginterferon alpha (peg-IFN-α) therapy and their association with hepatitis B surface antigen (HBsAg) clearance in inactive HBsAg carriers (IHCs).</p><p><strong>Methods: </strong>This prospective observational study enrolled 197 IHCs treated with peg-IFNα-2a/2b for 48 weeks and followed for 24 weeks (treatment group), and 221 IHCs who were regularly monitored for 72 weeks without treatment (IHC control group). Peripheral blood T lymphocyte subsets were evaluated using flow cytometry at baseline, and at 12, 24, 48, and 72 weeks in both groups. At 72 weeks, IHCs in the treatment group were categorized into an HBsAg clearance group and an HBsAg persistence group. Differences in T lymphocyte subsets among these groups were compared, and correlations between T lymphocyte subsets and HBsAg clearance were analyzed.</p><p><strong>Results: </strong>At 72 weeks, intention-to-treat analysis showed significantly higher HBsAg clearance (46.7%) and seroconversion rates (34.5%) in the treatment group compared to the IHC control group (HBsAg clearance rate of 1.4%, seroconversion rate of 0.9%; both <i>p</i> < 0.001). The median absolute counts of CD3⁺, CD4⁺, and CD8⁺ cells significantly decreased at 12, 24, and 48 weeks in both the HBsAg clearance and persistence groups, returning to baseline at 72 weeks (all <i>p</i> < 0.001). IHCs with HBsAg clearance had higher median percentages of CD3⁺ CD8⁺ cells and lower median percentages of CD3⁺ CD4⁺ cells and CD4⁺/CD8⁺ ratios at 12, 24, and 48 weeks compared to the HBsAg persistence and IHC control groups (all <i>p</i> < 0.001). Baseline HBsAg levels (below 2.0 log₁₀ IU/mL) and hepatitis B virus DNA levels (below 20 IU/mL), alanine aminotransferase elevation at 12 weeks (greater than 2×upper limit of normal), and CD4⁺/CD8⁺ ratios (less than 1.5 at 12 weeks and below 1.4 at 24 weeks) were predictive of HBsAg clearance.</p><p><strong>Conclusions: </strong>Peripheral blood CD4⁺/CD8⁺ ratios at 12 and 24 weeks may serve as predictive markers for HBsAg clearance in IHCs treated with peg-IFN-α.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 2","pages":"130-142"},"PeriodicalIF":3.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Extracellular Vesicle-derived MicroRNA Associated with Human Alpha-1 Antitrypsin Deficiency-mediated Liver Disease.","authors":"Regina Oshins, Zhiguang Huo, Zachary Greenberg, Virginia Clark, Sergio Duarte, Huiping Zhou, Jesse West, Mei He, Mark Brantly, Nazli Khodayari","doi":"10.14218/JCTH.2024.00253","DOIUrl":"10.14218/JCTH.2024.00253","url":null,"abstract":"<p><strong>Background and aims: </strong>Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with liver disease, ranging from fibrosis to hepatocellular carcinoma. The disease remains asymptomatic until its final stages when liver transplantation is the only available therapy. Biomarkers offer an advantage for disease evaluation. The presence of microRNAs (miRNAs) in plasma extracellular vesicles (EVs) presents a noninvasive approach to assess the molecular signatures of the disease. In this study, we aimed to identify miRNA biomarkers to distinguish molecular signatures of the liver disease associated with AATD in AATD individuals.</p><p><strong>Methods: </strong>Using small RNA sequencing and qPCR, we examined plasma EV miRNAs in healthy controls (n = 20) and AATD patients (n = 17). We compared the EV miRNAs of AATD individuals with and without liver disease, developing an approach for detecting liver disease. A set of miRNAs identified in the AATD testing cohort was validated in a separate cohort of AATD patients (n = 45).</p><p><strong>Results: </strong>We identified differential expression of 178 EV miRNAs in the plasma of the AATD testing cohort compared to controls. We categorized AATD individuals into those with and without liver disease, identifying 39 differentially expressed miRNAs. Six miRNAs were selected to test their ability to discriminate liver disease in AATD. These were validated for their specificity and sensitivity in an independent cohort of 45 AATD individuals. Our logistic model established composite scores with three- and four-miRNA combinations, achieving areas under the curve of 0.737 and 0.751, respectively, for predicting AATD liver disease.</p><p><strong>Conclusions: </strong>We introduce plasma EV-derived miRNAs as potential biomarkers for evaluating AATD liver disease. Plasma EV-associated miRNAs may represent a molecular signature of AATD liver disease and could serve as valuable tools for its detection and monitoring.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 2","pages":"118-129"},"PeriodicalIF":3.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of Coronary Artery Disease in Patients with Liver Cirrhosis: A Systematic Review and Meta-analysis.","authors":"Chunru Gu, Liyan Dong, Lu Chai, Zhenhua Tong, Fangbo Gao, Walter Ageno, Fernando Gomes Romeiro, Xingshun Qi","doi":"10.14218/JCTH.2024.00226","DOIUrl":"10.14218/JCTH.2024.00226","url":null,"abstract":"<p><strong>Background and aims: </strong>Coronary artery disease (CAD) is increasingly observed in patients with liver cirrhosis. However, data on the incidence and prevalence of CAD in cirrhotic patients are heterogeneous, and the association remains uncertain. In this study, we aimed to conduct a systematic review and meta-analysis to address these issues.</p><p><strong>Methods: </strong>PubMed, EMBASE, and Cochrane Library databases were searched. Incidence, prevalence, and factors associated with CAD were pooled using a random-effects model. Risk ratio (RR) and odds ratio (OR), with their 95% confidence interval (CI), were calculated to evaluate differences in CAD incidence and prevalence between patients with and without liver cirrhosis.</p><p><strong>Results: </strong>Fifty-one studies were included. The pooled incidences of CAD, acute coronary syndromes, and myocardial infarction (MI) were 2.28%, 2.02%, and 1.80%, respectively. Liver cirrhosis was not significantly associated with CAD incidence (RR = 0.77; 95% CI = 0.46-1.28) or MI (RR = 0.87; 95% CI = 0.49-1.57). The pooled prevalence of CAD, acute coronary syndromes, and MI was 18.87%, 12.54%, and 6.12%, respectively. Liver cirrhosis was not significantly associated with CAD prevalence (OR = 1.29; 95% CI = 0.83-2.01) or MI (OR = 0.58; 95% CI = 0.28-1.22). Non-alcoholic steatohepatitis, hepatitis C virus, advanced age, male sex, diabetes mellitus, hypertension, hyperlipidemia, smoking history, and family history of CAD were significantly associated with CAD in cirrhotic patients.</p><p><strong>Conclusions: </strong>CAD is common in cirrhotic patients, but cirrhosis itself may not be associated with an increased CAD risk. In addition to traditional risk factors, non-alcoholic steatohepatitis and hepatitis C virus infection are also associated with CAD presence in cirrhotic patients.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 2","pages":"93-104"},"PeriodicalIF":3.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferrochelatase Gene Variants Associated with Cholestasis in Adults: A Case Report.","authors":"Xiaona Lu, Kun Liu, Wenlan Zheng, Xuemei Zhang, Jia Shi, Shihan Yu, Yueqiu Gao, Hai Feng, Zhuo Yu","doi":"10.14218/JCTH.2024.00304","DOIUrl":"10.14218/JCTH.2024.00304","url":null,"abstract":"<p><p>We reported a case of recurrent liver dysfunction in an adult patient with a history of abnormal liver enzymes persisting for over ten years. The primary abnormalities included elevated levels of gamma-glutamyl transferase and alkaline phosphatase. Despite conducting a series of extensive etiological tests to identify common causes of liver disease, the diagnosis remained unclear. However, whole-exome next-generation sequencing revealed a homozygous intronic mutation in the ferrochelatase gene (c.315-48T>C), which may be associated with the patient's cholestasis.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 2","pages":"173-177"},"PeriodicalIF":3.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Significant Response to Palbociclib Plus Lenvatinib as Second-line Treatment for CDKN2A/2B Deletion Intrahepatic Cholangiocarcinoma: A Case Report.","authors":"Kai Liu, Ziyue Huang, Lijin Zhao, Haitao Zhao","doi":"10.14218/JCTH.2024.00404","DOIUrl":"10.14218/JCTH.2024.00404","url":null,"abstract":"<p><p>Cyclin-dependent kinase inhibitor 2A/2B (<i>CDKN2A/2B)</i> deletions are frequently identified in patients with biliary tract cancer; however, standard treatment options for this genetic alteration are lacking. Here, we present the case of a 64-year-old woman diagnosed with intrahepatic cholangiocarcinoma and hilar lymph node metastasis who underwent radical surgery. Postoperative pathology confirmed moderately differentiated adenocarcinoma. The tumor recurred during the second cycle of adjuvant chemotherapy following surgery, and the metastatic sites included the cranial region, right lung, and right adrenal gland. Genetic analysis revealed a <i>CDKN2A/2B</i> deletion, indicating palbociclib sensitivity. Subsequently, the patient received palbociclib plus lenvatinib as systemic therapy, along with stereotactic radiotherapy for the intracranial lesion. Notably, the right pulmonary metastasis significantly regressed after 12 months of treatment, with the complete disappearance of the intracranial tumor. However, the disease progressed at 32.2 months, with significant enlargement of the right adrenal gland metastasis and new metastasis in the right lung. The progression-free survival and overall survival were 32.2 months and 34.4 months, respectively. In conclusion, our case demonstrates that palbociclib plus lenvatinib is a promising chemotherapy-free second-line treatment for intrahepatic cholangiocarcinoma with a <i>CDKN2A/2B</i> deletion.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 2","pages":"169-172"},"PeriodicalIF":3.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Development and Appraisal of MELD 3.0 in Liver Diseases: Good Things Never Come Easy.","authors":"Gaoyue Guo, Wanting Yang, Jia Li, Ziyi Yang, Jing Liang, Chao Sun","doi":"10.14218/JCTH.2024.00303","DOIUrl":"10.14218/JCTH.2024.00303","url":null,"abstract":"<p><p>Since its proposal, the Model for End-Stage Liver Disease (MELD) score has been employed to predict short-term mortality among patients with chronic liver disease and those awaiting liver transplantation, serving as the primary criterion for organ allocation. However, as the demographic and epidemiological characteristics of chronic liver disease and liver transplantation have evolved, a range of MELD-related scores has emerged, including MELD-Na, iMELD, delta MELD, MELD XI, MELD-LA, and pediatric end-stage liver disease, culminating in the recently proposed MELD 3.0, which builds upon MELD-Na. This study aimed to comprehensively review and summarize relevant studies on MELD 3.0 in various scenarios, assessing its effectiveness in organ allocation, post-transplantation outcomes, and mortality prediction for patients with end-stage liver disease. Our preliminary findings indicate superior predictive performance of MELD 3.0, warranting further in-depth investigations to broaden its clinical implications.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 1","pages":"62-68"},"PeriodicalIF":3.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virological Response to Lamivudine and Tenofovir Treatment in a Mono-infected Chronic Hepatitis B Patient with Potential Tenofovir Resistance: A Case Report.","authors":"Monica Dahiya, Teresa Tai, Trana Hussaini, Gordon Ritchie, Nancy Matic, Eric M Yoshida, Christopher F Lowe","doi":"10.14218/JCTH.2024.00248","DOIUrl":"10.14218/JCTH.2024.00248","url":null,"abstract":"<p><p>Few cases of tenofovir resistance have been reported, and the appropriate treatment for such cases remains unclear. We aimed to share a case of a chronic hepatitis B mono-infected patient with potential tenofovir resistance who required combined lamivudine and tenofovir therapy to achieve adequate viral suppression. The patient's viral load (plasma) was monitored using the cobas® hepatitis B virus Test on the cobas® 6800 system. Hepatitis B antiviral drug resistance (AVDR) mutations were assessed by amplicon-based sequencing. Plasma was extracted using the MagNa Pure 24 system, and polymerase chain reaction targeting the polymerase gene (860bp) was performed. Sequencing was conducted on GridION R10.4.1 flow cells, and the resulting FASTQ files were analyzed using DeepChek®-HBV Software. We describe a female patient in her 60s with chronic hepatitis B who was e-antigen positive. She met treatment criteria in May 2020, when her alanine transaminase levels were 1.5 times above the upper limit of normal. She was initially started on entecavir but had to switch to tenofovir alafenamide in June 2020 due to a rash. Despite three years of tenofovir therapy, her viral load remained unsuppressed. AVDR testing identified two suspected tenofovir resistance mutations (V191I and A317S). Since no mutations associated with lamivudine resistance were detected, the patient was treated with a combination of lamivudine and tenofovir, achieving viral suppression after four months. Although rare, tenofovir resistance should be considered in patients with persistent viremia despite long-term therapy. AVDR sequencing facilitated the detection of potential tenofovir resistance and guided treatment decisions, leading to successful viral suppression in this case.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"13 1","pages":"84-87"},"PeriodicalIF":3.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}